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Protective effect o...
Protective effect of intermediate doses of hydrogen sulfide against myocardial ischemia-reperfusion injury in obese type 2 diabetic rats
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- Jeddi, Sajad (author)
- Shahid Beheshti University of Medical Sciences
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- Gheibi, Sevda (author)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups,Skåne University Hospital,Shahid Beheshti University of Medical Sciences
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- Kashfi, Khosrow (author)
- City University of New York
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- Carlström, Mattias (author)
- Karolinska Institutet,Karolinska Institute
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- Ghasemi, Asghar (author)
- Shahid Beheshti University of Medical Sciences
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(creator_code:org_t)
- Elsevier BV, 2020
- 2020
- English.
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In: Life Sciences. - : Elsevier BV. - 0024-3205 .- 1879-0631. ; 256
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Abstract
Subject headings
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- Objective: Subjects with type 2 diabetes (T2D) have lower circulating hydrogen sulfide (H2S) levels following myocardial ischemia and a higher risk of mortality. The aim of this study was to determine the dose-dependent favorable effects of sodium hydrosulfide (NaSH) on myocardial ischemia-reperfusion (IR) injury in rats with T2D. Methods: T2D was induced using a high-fat diet (HFD) and low-dose of streptozotocin. Rats were divided into control, T2D, and T2D + NaSH groups. NaSH (0.28, 0.56, 1.6, 2.8, and 5.6 mg/kg) was administered intraperitoneally for 9 weeks. At the end of the study, heart from all rats were isolated and left ventricular developed pressure (LVDP) and the peak rates of positive and negative changes in LV pressure (±dp/dt) were recorded during baseline and following myocardial IR injury. In addition, infarct size as well as mRNA expression of H2S- and nitric oxide (NO)-producing enzymes were measured. Results: In diabetic rats, NaSH only at doses of 0.56 and 1.6 mg/kg increased recovery of LVDP (16% and 42%), +dp/dt (25% and 35%) and –dp/dt (23% and 32%) as well as decreased infarct size (44% and 35%). At these doses, NaSH increased expressions of cystathionine γ-lyase (CSE) (440% and 271%) and endothelial NO synthase (eNOS) (232% and 148%) but it decreased the expressions of inducible NOS (iNOS) (55% and 71%). NaSH at 0.28, 2.8 and 5.6 mg/kg had no significant effects on these parameters. Conclusion: NaSH had a bell-shaped cardioprotective effect against myocardial IR injury in rats with T2D. Higher tolerance to IR injury in heart isolated from type 2 diabetic rats treated with intermediate doses of NaSH is associated with higher CSE-derived H2S and eNOS-derived NO as well as lower iNOS-derived NO.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- HS-producing enzymes
- Hydrogen sulfide
- Infarct size
- Ischemia-reperfusion injury
- NO-producing enzymes
- Type 2 diabetes
Publication and Content Type
- art (subject category)
- ref (subject category)
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